Infections of the Nervous System I

A Lecture Outline

© Hanuš Rozsypal
Meningism | Lumbar puncture | CSF examination | Bacterial meningitis


CLASSIFICATION OF NERVOUS SYSTEM INFECTIONS

A. Toxoinfectious encephalopathies

B. Infections of the nervous system

by localization of the disease process

  • central nervous system
    • meningitis
    • encephalitis
    • myelitis
  • peripheral nervous system
    • radiculitis
    • neuritis
  • combined involvement
    • meningoencephalitis
    • encephalomyelitis
    • polyradiculoneuritis

by character of the inflammatory response
  • purulent
  • aseptic
  • specific
by clinical course
  • acute
  • subacute
  • chronic

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MENINGISM

The meningism includes symptoms and signs which appear as a result of meningeal irritation by
  • inflammation
  • hemorrhage
  • neoplasm
  • increased intracranial pressure, high temperature etc.

Symptoms:

  • headache
  • vomiting
  • irritability, hyperesthesia, photophobia etc.

Signs:

  • meningeal signs

Meningeal signs

Meningeal signs

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LUMBAR PUNCTURE

LP is the investigation of choice in the diagnosis of meningitis.

Indications for LP:

  • To obtain CSF in a suspicion of meningitis
  • Reduction of raised intracranial pressure
  • Lumbar intrathecal instillation of drugs

Contraindications for LP:

  1. Mass lesion or very increased intracranial pressure (possible danger of herniation - tentorial or cerebellar coning) Some evidence for this circumstance are
    • rapidly developing depression of consciosness (coma)
    • focal neurologic signs
    • convulsions
    • papilledema.
  2. Significant coagulopathy (possible danger of bleeding)
  3. Infected lumbar area (possible danger of infection)

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CSF EXAMINATION

ROUTINE INITIAL STUDIES

  • Cytology
    • cell count

Fuchs-Rosenthal´s counting chamber

Fuchs-Rosenthal´s counting chamber (volume 3 ml)

  • Chemistry
    • protein
    • glucose
    • chloride

ROUTINE TESTS according to results of initial studies

     If purulent CSF pattern:
  • Microbiology:
    • Gram´s staining
    • latex agglutination
    • bacterial cultures
     If aseptic CSF pattern:
  • Serologic tests:
    • Lyme disease serology
SPECIAL STUDIES according to results of routine tests

     If special suspicion:
  • Cytology:
    • smear of the sediment
    • immunocytology
  • Chemistry:
    • lactic acid
    • colloidal gold curve
    • oligoclonal bands
    • immunoglobulins
  • Microbiology:
    • india ink
    • fungal cultures
    • mycobacterial studies
    • electron microscopy (Borrelia burgdorferi)
  • Virology:
    • viral cultures
    • PCR
    • electron microscopy (JCV)
  • Serologic tests:
    • syphilis serology


CSF FINDINGS

Crucial CSF findings

Typical CSF findings

Test

 

Item

 

Pattern 

Normal Purulent Aseptic
Appearance

 

pellucid turbid pellucid or haze
Cytology Cell count (/3ml) <10/3 1000-100000/3 10-1000/3
Predominant cells lymphocytes polymorphonuclears lymphocytes
Chemistry Protein 0,1-0,4 g/l 3-4 g/l and more 0,4-1,0 g/l
Glucose normal low normal
Lactate normal high normal
Chloride normal normal normal
Microbiology Gram stain negative positive (often) negative
Latex agglutination negative positive (usually) negative
Bacterial culture negative positive (often) negative

Other CSF findings

Guillain-Barré syndrome:

  • Cell count: normal or low lymphocytar pleocytosis (<50/3ml)
  • Protein: high (usually about 1g/l)
  • Glucose: normal
  • Chloride: normal
Fungal or tuberculous meningitis:

  • Cell count: low mixed pleocytosis
  • Protein: high
  • Glucose: low
  • Chloride: low
Parameningeal inflammatory focus (brain abscess, endocarditis):

  • Cell count: low mixed or polymorphonuclear pleocytosis
  • Protein: high
  • Glucose: normal
  • Chloride: normal

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BACTERIAL MENINGITIS
Meningitis purulenta

Incidence: 3-4/100.000

Etiology:

  Major causative organisms (90%)

  • Streptococcus pneumoniae (pneumococcus)
  • Neisseria meningitidis (meningococcus)
  • Haemophilus influenzae
Epidemiology: most diseases - sporadic, meningococci A et C - epidemic too

Pathophysiology:

  routes of infection

  • hematogenous
  • per continuitatem
  • direct invasion (penetrating head trauma, meningomyelocele)

Meningitis

  1. Primary
  2. Secundary
    • pneumonia (pneumococcus)
    • head trauma - penetrating or closed (pneumococcus, staphylococcus, G- bacilli)
    • chronic otitis media (pneumococcus)
    • sinusitis (pneumococcus, Haemophilus)
    • neurosurgery (G- bacilli, staphylococcus, anaerobes, Nocardia)
    • CSF shunt (Staphylococcus epidermidis, S. aureus, G- bacilli, diphteroids)

Clinical manifestations:

Symptoms:

  • rapid onset
  • fever
  • headache
  • vomiting
  • confusion
  • others: seizures, skin rash, myalgias

Signs:
  • fever
  • meningismus
  • skin rash (petechiae)
  • other neurologic and related findings
    • altered consciousness
    • cranial nerve palsies
    • signs of increased intracranial pressure (HR, BP, breathing, cranial nerves involvement)
    • focal neurologic signs (hemiparesis, aphasia)
  • other complaints
    • herpes labialis
    • signs of shock

Tests:

  • ESR: very high
  • BC: leucocytosis
  • CRP: very high
  • CSF: polymorphonuclear pleocytosis, high protein level, hypoglycorrhachia

Course:

   acute - fulminant

Complications and sequelae:

Complications:

Intracranial complications:
  • cerebral abscess
  • subdural and epidural empyema
  • thrombophlebitis of venous sinus
  • subdural effusion (hygroma subdurale)
  • obstructive hydrocephalus

Normal CT Scan Cerebral Abscess
Purulent Meningitis
(Normal CT Scan)
Cerebral Abscess *
Epidural Empyema Subdural Effusion
Epidural Empyema * Subdural Effusion **
Obstructive Hydrocephalus Pneumocephalus
Obstructive Hydrocephalus Pneumocephalus

        Sources of pictures:
  • * Duniewicz M, Adam P, et al. Neuroinfekce. Maxdorf, Praha 1999, pp.309
  • ** Táborská J, Koubová A, Valchová M. Hemofilové meningitidy u dětí do pěti let věku. Čes-slov Pediat 2002;57(3):91-100

Other neurologic sequelae:
  • cranial nerve palsies
  • motoric involvement (for example hemi- or quadruparesis, ataxia)

Specific complications of meningococcaemia:
  • myocarditis
  • pericarditis
  • metastatic or reactive arthritis
  • disseminated intravascular coagulopathy (DIC)
  • Watterhouse-Friderichsen´s syndrome
Non-specific complications:
  • pneumonia
  • urinary tract infections (UTI)
  • intravenous catheter-related bacteremia or sepsis
  • fever (>4 days)

Sequelae:

  • behavioral disturbances, mental retardation
  • visual problems
  • hearing loss (deafness)
  • motoric involvement (permanent paralysis)
  • secundar epilepsy

Diagnosis:

  • History: chronic otitis media and head trauma.
  • Symptoms and signs: fever, headache, meningism and signs of cerebral dysfunction (declining level of consciousness).
  • Laboratory data: CSF - pyogenic formula, ESR, BC, CRP - consistent with bacterial infection
  • Additional examinations:
    • Hemocoagulation
    • Chemistry
    • Blood cultures
    • Fundoscopy (because excluding of papilledema)
    • ENT exam
    • X-ray (of chest, skull, mastoids, sinuses)
    • CT scans, MRI, brain ultrasonography (in infancy)
    • Audiogram
    • Radioisotopic scanning

Differential diagnosis:

  • Non-bacterial meningitis (aseptic, tuberculous, fungal)
  • Brain abscess
  • Intracranial or spinal epidural abscess/ empyema
  • Subdural empyema
  • Bacterial endocarditis with embolism
  • Thrombophlebitis of venous sinus
  • Ruptured dermoid cysts
  • Brain tumors
Prognosis: serious.

     Mortality: 10-20% (despite therapy!)
     Prognosis depends upon many factors, including the following:
  • the causative microorganism
  • the age of the patient
  • the underlying diseases

Treatment:

  1. Antimicrobial agents:

Age group Common pathogens Suggested regimens Comments
Newborn G- enteric bacilli, streptococci gr. B, D, Listeria monocytogenes cefotaxime + ampicillin  
Infant 1-3 months H. influenzae, S. pneumoniae, N. meningitidis, G- enteric bacilli, streptococci gr. B,D, L. monocytogenes ceftriaxone/ cefotaxime + ampicillin USA: + vancomycin *)
Infant 3 months to child to 7 years H. influenzae, S. pneumoniae, N. meningitidis ceftriaxone/ cefotaxime USA: (+ vancomycin)
Ages 7-50 years N. meningitidis, S. pneumoniae, L. monocytogenes ceftriaxone/ cefotaxime or chloramphenicol aqueous penicillin if dg. meningococcal meningitis is most-likely
USA: (+ vancomycin)
Adult more than 50 years S. pneumoniae, G- enteric bacilli, P. aeruginosa, L. monocytogenes ceftriaxone/ cefotaxime (+ampicillin) USA: (+ vancomycin)

*) high prevalence of high-level drug-resistant S. pneumoniae (DRSP)


Predisposing factor Common pathogens Suggested regimens Comments
Alcoholism or other debilitating disease S. pneumoniae, G- enteric bacilli, P. aeruginosa, L. monocytogenes ceftriaxone/ cefotaxime (+ ampicillin) USA: (+ vancomycin)
Head trauma, post-neurosurgery S. pneumoniae, S. aureus, G- enteric bacilli, P. aeruginosa chloramphenicol USA: vancomycin + ceftazidim
Ventriculo-peritoneal or ventriculo-atrial shunt S. epidermidis, S. aureus, G- enteric bacilli, Propionibacterium acnes vancomycin + rifampicin or 3rd-gen. cephalosporin  
Chronic meningitis M. tuberculosis, C. neoformans, neoplasm No urgent empiric therapy  
HIV positive C. neoformans, M. tuberculosis, T. pallidum, L. monocytogenes, S. pneumoniae, H. influenzae ceftriaxone/ cefotaxime + ampicillin (+amphotericin B)  

  1. Reduction of intracranial pressure:

    • Mannitol 20% (0.25g/kg q4-6h IV = 1.0-1.5ml/kg q4-6h IV)
    • Dexamethasone (0.15mg/kg q4-6h IV)
    • (Hyperventilation)

  2. Other supportive care and symptom-based therapy

    • Infusions
    • Antipyretics
    • Anticonvulsants
    • Mechanical ventilation

  3. Treatment of complications

Prevention and prophylaxis:

Vaccination

  • H. influenzae: H. influenzae type b (Hib) conjugate vaccine
  • N. meningitidis: quadrivalent meningococcal vaccine (active against serogroups A, C, Y, and W135)
  • S. pneumoniae: 23-valent pneumococcal vaccine
  • S. agalactiae: not possible
  • Basilar skull fracture: 23-valent pneumococcal vaccine (?)

Chemoprophylaxis

  • H. influenzae: (rifampicin)
  • N. meningitidis: penicillin, co-trimoxazole, macrolids, rifampicin, ceftriaxone, ciprofloxacin
  • S. pneumoniae: (penicillin, rifampicin)
  • S. agalactiae: (ampicillin or penicillin intra partum)
  • Basilar skull fracture: not recommended (?)


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© H. Rozsypal
The page was last updated 20-April-2004